Rapamycin enhances the anti-angiogenesis and anti-proliferation ability of YM155 in oral squamous cell carcinoma

Tumour Biol. 2017 Jun;39(6):1010428317706213. doi: 10.1177/1010428317706213.

Abstract

YM155, a small molecule inhibitor of survivin, has been studied in many tumors. It has been shown that YM155 inhibited oral squamous cell carcinoma through promoting apoptosis and autophagy and inhibiting proliferation. It was found that YM155 also inhibited the oral squamous cell carcinoma-mediated angiogenesis through the inactivation of the mammalian target of rapamycin pathway. Rapamycin, a mammalian target of rapamycin inhibitor, played an important role in the proliferation and angiogenesis of oral squamous cell carcinoma cell lines. In our study, cell proliferation assay, transwell assay, tube formation assay, and western blot assay were used to investigate the synergistic effect of rapamycin on YM155 in oral squamous cell carcinoma. Either in vitro or in vivo, rapamycin and YM155 exerted a synergistic effect on the inhibition of survivin and vascular endothelial growth factor through mammalian target of rapamycin pathway. Overall, our results revealed that low-dose rapamycin strongly promoted the sensitivity of oral squamous cell carcinoma cell lines to YM155.

Keywords: Rapamycin; YM155; angiogenesis; oral squamous cell carcinoma; proliferation.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Imidazoles / administration & dosage*
  • Inhibitor of Apoptosis Proteins / biosynthesis
  • Mice
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Naphthoquinones / administration & dosage*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Sirolimus / administration & dosage*
  • Survivin
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Xenograft Model Antitumor Assays

Substances

  • BIRC5 protein, human
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • Naphthoquinones
  • Survivin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • YM 155
  • Sirolimus